All non-sensory pertussis toxin sensitive G protein alpha subunits have been knocked out in earlier years by gene targeting. Previously we had found that Gi2 KO mice develop ulcerative colitis (UC) in 129Sv mice but not C57BL mice, and that Go KO mice develop a turning syndrome. In collaborative studies we also noted that expression of Go-alpha blocks cAMP-induced neurite outgrowth. During this year we discovered that Gi2 KO mice have a defect in cerebellar foliation, that the Gi2-alpha subunit has an intrinsic cardioprotective effect (in collaboration with Stefan Herzig), and that it plays a role in B cell development leading to a decrease in T2 transitional B cells as well as B-1a B cells. We have now backcrossed the Gi2 mutation form 129SV to C57BL/6J and are beginning the breeding program to map the modifier gene affecting expression of the UC. We are constructing Go1-alpha minigene vectors for transgenic expression in defined subsets of neurons based on the neurotransmitter they release.